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Expression of Endothelin-1 and Its Receptors in Cisplatin-Induced Acute Renal Failure in Mice

机译:内皮素-1及其受体在顺铂诱导的小鼠急性肾衰竭中的表达

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摘要

Endothelin-1 (ET-1) is unequivocally elevated in the kidney with ischemic acute renal failure (ARF), whereas ET receptors (ETAR and ETBR) are variably expressed. Although renal functional and structural changes are similar between ischemic and nephrotoxic ARF, there are few reports on the alteration in the ET system in nephrotoxic ARF. This study was, therefore, undertaken to investigate changes in renal expression of ET-1 and its receptors in nephrotoxic ARF induced by cisplatin. Mice were intraperitoneally injected with 16 mg of cisplatin/kg at a single dose, and the expression of mRNA and protein was then quantified by real-time RT-PCR and Western blot, respectively. Immunohistochemistry was conducted for localization. Three days after treatment, ET-1 transcript in cisplatin-treated mice was thirteen times higher than that in controls, whereas ET-1 peptide was increased by 1.5-fold. Cisplatin caused a 2-fold increase in the levels of ETAR mRNA and protein. Most of the increased immunoreactive ET-1 and ETAR were localized in damaged tubules. Neither the expression of ETBR mRNA nor the abundance and immunoreactive level of ETBR protein were changed. The findings suggest that the individual components of the renal ET system are differentially regulated in cisplatin-induced nephrotoxic ARF.
机译:在患有缺血性急性肾衰竭(ARF)的肾脏中,内皮素-1(ET-1)明显升高,而ET受体(ETAR和ETBR)的表达却不同。尽管肾功能和肾毒性ARF之间的肾功能和结构变化相似,但关于肾毒性ARF中ET系统改变的报道很少。因此,本研究旨在研究顺铂诱导的肾毒性ARF中ET-1及其受体的肾脏表达变化。一次腹膜内注射小鼠16 mg顺铂/ kg,然后分别通过实时RT-PCR和Western blot定量mRNA和蛋白的表达。进行免疫组织化学定位。处理三天后,顺铂处理的小鼠中的ET-1转录物比对照组高13倍,而ET-1肽增加了1.5倍。顺铂使ETAR mRNA和蛋白质水平增加了2倍。大部分增加的免疫反应性ET-1和ETAR定位在受损的肾小管中。 ETBR mRNA的表达以及ETBR蛋白的丰度和免疫反应水平均未改变。这些发现表明,在顺铂诱导的肾毒性ARF中,肾脏ET系统​​的各个组成部分受到不同的调节。

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